The Use of Prostaglandin F2 Alpha in Selective Hepatic Angiography 1

Diagnostic Radiology

David Legge, M.B., F.R.C.R. Comparison has been made between slow infusion hepatic angiographic studies obtained before and after the intra-arterial injection of prostaglandin F2 alpha. The prostaglandin injection resulted in increased caliber of the hepatic arteries, increased opacification of the parenchyma of the liver and improved visualization of the wall of the gallbladder. Poorly vascularized metastatic lesions were better shown on the prostaglandin studies, and carcinoma of the gallbladder was diagnosed in two instances. The demonstration of highly vascularized metastatic tumor was enhanced on the prostaglandin studies, but further improved after the injection of angiotensin. INDEX TERMS: (Hepatic artery, arteriography 9 [52]. 1222). (Hepatic artery, vasodilator adjunct 9 [52]. 1272) • Liver neoplasms, angiography • Prostaglandin

Radiology 124:331-335, August 1977

selective hepatic angiography is an established technique for the demonstration of tumors involving the liver, certain metastatic lesions are poorly vascularized and may only be diagnosed with good reliability after they reach 2-5 cm in size (1). Such poorly vascularized metastatic lesions are shown on hepatic angiographic studies by displacement of the intrahepatic arteries, or by the presence of radiolucent filling defects within the parenchyma of the liver. We have attempted to improve opacification of the parenchyma of the liver by the use of a vasodilator, prostaglandin F2 alpha", on the premise that improved hepatic opacification should allow better demonstration of poorly vascularized metastatic tumor. This paper describes experience with our technique.

MATERIAL AND METHOD

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Between April 1975 and August 1976,50 patients were examined by selective hepatic angiography with prostaglandin F2 alpha. Fifty milliliters of Hypaque 65 % (iodine content 0.39 g/ml) was injected into the hepatic artery before and immediately after the injection of 60 micrograms of prostaglandin F2 alpha. The contrast medium was infused into the hepatic artery over a 15-20 second period. At least ten minutes elapsed between injections in order to avoid any residual vasodilitation from the first contrast injection. In 10 instances, both slow (3-4 ml/sec.) and fast (8-10 ml/sec.) injection rates of contrast medium were used immediately after the injection of prostaglandin F2 alpha. Twenty-five patients were referred for angiographic

Fig. 1. A. Normal selective hepatic study of 56-year-old man. B. Hepatic study after intra-arterial injection of 60 micrograms of prostaglandin F2 alpha, which gives increased opacification of the parenchyma of the liver. 1 From the Department of Radiology, Mater Misericordiae Hospital, Dublin, Ireland. Presented at the Sixty-second Scientific Assembly and Annual Meeting of the Radiological Society of North America, Chicago, III., Nov. 14-19, 1976. shan 2 Upjohn Ltd.

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normal studies, 12 showed metastatic involvement of the liver; in one of these patients, and one other, carcinoma of the gallbladder was diagnosed. One patient had hepatitis, one cirrhosis of the liver, and one dilatation of the intrahepatic bile ducts due to obstruction by carcinoma of the head of the pancreas. Normal Studies In all instances, comparison of the normal study with the study using prostaglandin showed an increased calibre of the intrahepatic and cystic arteries and opacification of smaller intrahepatic vessels, following injection of prostaglandin. On later films of the prostaglandin series, opacification of the liver was increased significantly (Fig. 1). In most cases, a fine granular appearance in the liver was produced (Fig. 2). The left lobe of the liver was also better shown. Where present, the wall of the gallbladder was well opacified. This was only poorly seen in the studies without prostaglandin and in some of these studies was not shown at all. Metastatic Lesions

Fig. 2. Normal prostaglandin study of 52-year-old man, showing intense opacification of the parenchyma of the liver which has a fine granular appearance. The wall of the gallbladder and also the duodenum are well opacified.

studies of the liver to determine metastatic involvement from a known or suspected primary tumor, 4 were examined for abdominal trauma, and 3 were referred for evaluation of hepatic cirrhosis. The remaining 18 patients had been referred for pancreatic or mesenteric angiography, and hepatic injections were made on completion of these studies. Since completing the series of 50 patients .we no longer obtain control films and now use prostaglandin routinely in all of our selective hepatic studies. However, in 15 cases we have reversed the order of injection, obtaining a control series at least 15 minutes after the prostaglandin study. In each instance, hepatic opacification was better in the series obtained immediately after the prostaglandin injection. RESULTS

Thirty-four hepatic studies were normal. Of the 16 ab-

Three of the metastatic lesions arose from the pancreas, five from the colon, one from the gallbladder, one from the pelvis, one from carcinoid tumor in the ileum, and one from the kidney. All but the renal carcinoma and carcinoid tumor were poorly vascularized. In all instances, the use of prostaglandin improved the demonstration of the hepatic involvement and demonstrated smaller metastatic deposits which were not shown without the drug (Fig. 3). The poorly vascularized metastatic lesions were well demonstrated against the densely opacified hepatic parenchyma. Visualization of the two highly vascular metastatic tumors was improved by the use of prostaglandin but, as expected, was dramatically improved by the use of angiotensin (Fig. 4). No false-negative studies were found in this series and in 5 patients who had no angiographic evidence of hepatic metastases, and who were treated surgically for gastrointestinal carcinoma, there was no hepatic involvement found at operation nor on biopsy of the liver taken at operation. Carcinoma of the Gallbladder Both cases of carcinoma of the gallbladder were readily demonstrated on the prostaglandin studies. The cystic artery and its branches were better visualized and the presence of irregular tumor vessels diagnosed. As with the normal prostaglandin studies, the wall of the gallbladder was well opacified but was shown to be irregular and thickened, containing tumor vessels (Fig. 5). In the 10 patients in whom comparison was made between the slow and fast injection rates of contrast medium, significantly better opacification of the liver and gallbladder was achieved with the slow injection technique. No side effects were noted after the injection of prostaglandin and no fall in blood pressure was recorded.

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Fig. 3. A. Control study of a patient with metastatic carcinoma from the colon showing a poorly vascularized mass near the hilus of the liver. B. Prostaglandin study: The mass is better defined against the densely opacified hepatic parenchyma and there are several smaller areas of poorly vascularized metastases.

COMMENT

The prostaglandins are a group of biologically active fatty acids, thought to be involved in several regulatory mechanisms in man. They have the property of relaxing vascular smooth muscle, and when injected intra-arterially produce local vasodilatation. Prostaglandin E1 has been studied in the splanchnic circulation of dogs by Davis et al. (2), while prostaglandin F2 alpha has been used for superior mesenteric angiography in man by Dencker et al. (3). In both studies, local blood flow was increased by more than 100 % and no systemic hemodynamic changes were noted. The improved hepatic opacification in our series is more likely due to vasodilatation of smaller vessels than to the increased flow, since increasing the pressure of injection of contrast medium did not improve the opacification of the liver. The angiographic diagnosis of poorly vascularized hepatic metastases has always been difficult and has been associated with a high diagnostic error rate (7). Prostaglandin appears to improve the quality of hepatic studies, yet there has been little emphasis on the use of vasodilator drugs in selective hepatic angiography. Recently, Goldstein et al. (4) have described their experience using tolazoline in hepatic angiography and improved visualization of hepatic metastases by enhancing the vascularity of the lesions. We have improved the visualization of poorly vascularized hepatic metastases by increasing the density of

the liver so that the lesions could be shown as negative defects even if no "rim effect" is present. A slow infusion technique as described by Kaude et al. (5) was preferred for our studies compared to the 4-5 second injection period used by Goldstein. A striking additional feature of the studies using prostaglandin was increased opacification of the cystic artery and its branches, and thus of the wall of the gallbladder. It is established that angiography is the only means of demonstrating carcinoma of the gallbladder before operation (6). The improved anatomic detail obtained after injection of prostaglandin resulted in the correct diagnosis of both of our cases of carcinoma of the gallbladder. Goldstein et al. (4) recommend the use of tolazoline in situations in which the hepatic angiographic study appears normal in spite of positive clinical findings or positive radioisotope scan, where it is equivocal or where the full extent of the hepatic disease must be assessed. Because the quality of all our hepatic studies was improved by the use of prostaglandin, we no longer obtain a control series and now use this drug routinely in all of our selective hepatic studies; if a highly vascular hepatic tumor is suspected, angiotensin is used first since it has a much shorter duration of action than prostaglandin. The use of slow infusion hepatic angiography, augmented by prostaglandin, should reduce the diagnostic error rate for poorly vascularized hepatic tumors, and should aid the preoperative diagnosis of carcinoma of the gallbladder.

Fig. 4. A. Control study of a 46-year-old man who had a highly vascular renal cell carcinoma, showing large poorly defined tumor in the superior aspect of the liver. B. Prostaglandin study: The vascularity of the lesion is enhanced and the margin is better shown. C. Further improvement in the demonstration of the tumor after the injection of 1 microgram of angiotensin.

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Fig. 5. A. Control study of 64-year-old jaundiced patient, with poor and uneven opacification of the parenchyma of the liver and poor demonstration of the gallbladder. B. The prostaglandin study shows irregular thickening of the wall of the gallbladder and poorly vascularized metastatic tumor in the adjacent liver.

REFERENCES 1. Bartley 0, Helander CG, Rosengren B, et al: Scintigraphy and angiography in demonstration of hepatic tumours. Acta Radiol [Diag] 8:161-167, Mar 1969 2. Davis LJ, Anderson JH, Wallace S, et al: The use of prostaglandin E1 to enhance the angiographic visualization of the splanchnic circulation. Radiology 114:281-286, Feb 1975 3. Dencker H, G6thlin J, Hedner P, et al: Superior mesenteric angiography and blood flow following intra-arterial injections of prostaglandin F2 alpha. Am J RoentgenoI125:111-118, Sep 1975 4. Goldstein HM, Thaggard A, Wallace S, et al: Priscoline-augmented hepatic angiography. Radiology 119:275-279, May 1976

5. Kaude J, Jensen R, Wirtanen GW: Slow injection hepatic angiography. Acta Radiol [Diag] 14:700-712, Nov 1973 6. Pettersson H: Carcinoma of the gallbladder-a review of 158 cases. Acta Radiol [Diag] 15:225-236, Mar 1974 7. Watson RC, Baltaxe HA: The angiographic appearance of primary and secondary tumors of the liver. Radiology 101:539-548, Dec 1971

David Legge, M.B., F.R.C.R. Department of Radiology Mater Misericordiae Hospital Dublin, Ireland

The use of prostaglandin F2 alpha in selective hepatic angiography.

The Use of Prostaglandin F2 Alpha in Selective Hepatic Angiography 1 Diagnostic Radiology David Legge, M.B., F.R.C.R. Comparison has been made betwe...
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